Antibiotics Basics

Question 1

This card deck will be about the basics of antibiotics as well as some general terminology. First what is chemotherapy?

Answer 1

Tx of a disease by a chemical compound selectively directed against invading microbes or abnormal cells

Question 2

What is the definition of antibiotic?

Answer 2

Microbial product or its derivative that kills or inhibits growth of a susceptible microorganism

Question 3

What is the difference between an antimicrobial and an antibacterial?

Answer 3

Antimicrobial: any agent that kills or inhibits growth of a susceptible microorganism
Antibacterial: any agent that kills or inhibits growth of susceptible bacteria

Question 4

What is the difference between bacteriostatic vs bactericidal?

Answer 4

Bacteriostatic: reversible inhibition of growth
Bactericidal: irreversible inhibition of growth

Question 5

What is selective toxicity?

Answer 5

Ability to injury or kill an invading microorganism without harming host cells

Question 6

What are the various spectrum of antibiotics?

Answer 6

Broad: antimicrobial drugs which are effective against several groups of microorganisms
Narrow: antimicrobial drugs which are effective against only a few groups of microorganism
Extended: antimicrobial drugs that are effective against Gram + organisms and a significant number of Gram - organisms

Question 7

Finally what is postantibiotic effect?

Answer 7

When the killing action of an antimicrobial agent continues once drug plasma levels are below measurable levels

• -may reflect lag time by bacteria to synthesize new enzymes and cellular components
• -persistence of an antimicrobial agent at the target site
• -enhanced susceptibility of the bacteria to phagocytic and other defense mechanisms

Question 8

Next topic is on Minimal Inhibitory Concentration (MIC). What is this?

Answer 8

Lowest concentration of an antibiotic that prevents visible growth of the bacteria
—the clinically obtainable antibiotic concentration should be greater than the MIC

Question 9

What are the two ways to measure MIC?

Answer 9

1. Broth or tube dilution method
   - –serial two fold dilutions of the antibiotic are made in a liquid growth medium which is inoculated with a standardized number of organisms and incubated. the lowest concentration of antibiotic preventing appearance of turbidity is considered to be the MIC.
2. Disk Sensitivity Test: inhibition of reproduction of a microorganism on the surface of a solid medium by an antimicrobial agent which diffuses into the medium from a filter paper disk.

Question 10

Next topic is Minimal Bactericidal Concentration (MBC). What is this test?

Answer 10

Performed in conjunction with MIC by dilution method
–from each MIC broth tube without evidence of visible growth, an aliquot of the broth is spread across the entire surface of an agar plate.
–after overnight incubation, the MBC plates are examined for colony growth or lack of growth for each dilution subcultered.
No growth = antibiotic was bactericidal at that dilution
Growth = antibiotic was bacteriostatic at that dilution
MBC = lowest concentration of an antibiotic that results in no growth

Question 11

Moving on to Antimicrobial Combination Therapy. What is this?

Answer 11

Use of multiple drugs to treat an infection

Question 12

What are the reasons for using Antimicrobial Combination Therapy?

Answer 12

1. Emergency Situations
2. Infections are known or thought to be caused by multiple organisms
3. To achieve synergistic effects.
4. To prevent emergency of drug resistance organisms.
5. To treat patients whose immune system is suppressed

Question 13

What is a disadvantage of combination therapy?

Answer 13

Some agents only act on multiplying bacteria

–if these agents are combined with another agent that causes bacteriostasis they will be less effective

Question 14

So how do you choose the right agent? There are a number of ways. The first is to identify the organism. How is this done?

Answer 14

Gram stain
–allows differentiation of bacteria in two groups based on their cell wall properties
Gram Positive: thick peptidoglycan layer (purple)
Gram Negative: thin cell wall (pink)

Question 15

What are the pros gram stain to identify the organism?

Answer 15

Pros:

• useful tool in identifying the presence and morphologic features of the infecting organism in samples of sterile body fluids
• -gram stain provides important information when knowledge of an infection would make an important difference in the patients treatment and prognosis

Question 16

The next way in deciding the right agent is empiric therapy. What doe this mean?

Answer 16

Given when immediate therapy is required and there is no time to wait for cultures
–drug choice is based on site of infection and patients history.

Question 17

The third way in deciding the right agent is looking at the effect of site of infection on therapy. Whether a drug can access the site of infection is an important factor. For example not all drugs can penetrate the BBB. Penetration of the BBB is influenced by what factors?

Answer 17

1. Lipid solubility of a drug: more lipid soluble a drug, easier it can cross the BBB
2. Molecular Weight: larger a drug the less likely it is to penetrate the BBB
3. Protein Binding of a drug: Plasma protein binding reduces the free drug concentration available for BBB penetration

Question 18

The fourth way in deciding the right agent is patient factors. There are a number of patient factors that modify the response to a particular drug. What are these?

Answer 18

1. Immune System: if person is immunocompromised they need to be treated aggressively. Also keep in mind there is a higher likelihood that they can have hospital acquired infection. Also bacteriostatic drugs may not be sufficient in these patients
2. Renal or hepatic dysfunction: metabolism/clearance of a drug can be substantially altered by a decrease in either liver or kidney function
3. Poor perfusion: a decrease in perfusion will alter the kinetics of a drug
4. Age: decrease in kidney and liver functions. also kids are treated differently
5. Pregnancy and lactation: potential teratogenic effects

Question 19

The fifth way in deciding the right agent is safety of the agent. What does this mean?

Answer 19

Safest agents are the ones that are most selective towards bacteria
–able to slow the growth or kill the bacteria without having any effect on the host

Question 20

The sixth way in deciding the right agent is cost of therapy. What does this involve?

Answer 20

Drugs with similar efficacy can differ dramatically in price

Question 21

The last way in deciding the right agent is route of administration. What does this involve?

Answer 21

Depends on the type of infection
–mild: oral or topical
–serious: parenteral
Drugs also have very poor absorption from the GI tract
–they are not effective then when given orally

Question 22

Briefly we will discuss antimicrobial resistance which is said to have occurred when the maximal level of an antibiotic tolerated by the host does not halt growth of the bacteria. What are the different mechanisms from which resistance can be acquired?

Answer 22

1. Spontaneous mutations of DNA
2. DNA transfer of drug resistance
3. Altered expression of proteins in drug resistant organisms

Question 23

Next briefly there are a number of common complications that occur in a host due to antibiotic therapy. What are these complications?

Answer 23

1. Hypersensitivity reactions occur relatively frequently
2. Direct toxicity occur when the antimicrobials directly affect the hosts cellular processes
3. Superinfections are when a new or secondary infection occurs during the treatment of a primary infection with antimicrobials

Question 24

Again another brief topic to touch on is Antimicrobial chemoprophylaxis. It is not recommended in all situations in order to reduce the development of drug resistance. What are the guidelines?

Answer 24

1. Chemoprophylaxis should always be directed towards a specific pathogen (drug with the narrowest spectrum)
2. No drug resistance should develop
3. Use of the chosen drug should be limited duration
4. Conventional therapeutic doses should be employed (important drugs are given above their MIC or MBC)
5. Chemoprophlyaxis should only be used in situations of documented drug efficacy.